The subject of the present proposal has a strong interdisciplinary character, being situated at the interface between chemistry, physics and biology. The main research direction will be focused on the interactions between the surface relief profile of the cells substrate and the cells response (cell fate) to the mechanical signals induced by the substrate. In the last period more and more biological studies were dedicated to this problem, especially in the case of stem cells, taking into consideration the possibility of cells differentiation using only mechanical signals. In the tissue engineering this type of interactions between the substrate and the cells will be decisive for the fabrication of smart biomaterials. Ideal candidates for new types of cells’ supports are the azo-polymers, because in their case one can change the film surface configuration, elasticity, or other mechanical parameters using only the light as external stimulus. All the other external stimuli usually used for the modification of the mechanical properties of a material (pH, temperature, salts concentration etc.) will affect the cell function making difficult to understand the cells’ response. In the case of azo-polymers, using a polarized laser source one can generate surface relief gratings on the film surface. The geometrical parameters of the gratings (amplitude and periodicity) can be very well controlled through laser operational conditions. Different chemical structure of the azo-groups will be synthesized in order to evaluate the cells adhesion capacity and the cells fate, as a function of the relief characteristics. More of than the surface relief type (grating or islands) can be changed in contact with water, creating so-called dynamic surfaces.
| Name | Academic/ scientific title |
|---|---|
| Hurduc Nicolae | Professor, SR I |
| Scutaru Dan | Professor, SR I |
| Ibanescu Constanta | Professor, SR I |
| Carlescu Irina | Associate professor, SR II |
| Epure Elena-Luiza | Lecturer, SR III |
| Herghiligiu Cristina-Maria | Assistant professor, SR |
| Nichita Norica | Researcher, SR I |
| Petris Adrian | Researcher, SR I |
| Gheorghe Petronela | Researcher, SR |
| Ciobotarescu Simona | PHD student |
| Constantinel Roxana | PHD student |
| Caluian Andreea | Masters student |
| Iorga Sandra-Teodora | Masters student |
| Petrisor Amalia | Masters student |
Stage 1: Synthesis, characterization and molecular modeling of azo-polymers having flexible or rigid main-chain, as biological photo-active supports.(12/07/2017 - 31/12/2017)
Task 1.1 - Molecular modeling studies of proposed azo-polymers.
Task 1.2 - Synthesis and characterization of azo-polymers having flexible or rigid chains, substituted with different azogroups.
Stage 2: Investigation and promotion of interactions at the azo-polymer film and biological environment interfaces.(01/01/2018 - 31/12/2018)
Task 2.1 - Evaluation of surface properties in biological conditions of azo-polysiloxanes with varying glass transition temperatures (Tg).
Task 2.2 - Interface compatibility with cell cultures.
Task 2.3 - Evaluation nanostructuration processes of azo-polymeric films using pulse or continuous laser irradiation
Stage 3: Investigation of the extra cellular matrix influence on cell cultures development with azo-polymers having a stable and dynamic surface relief; the study of the effect induced by the trans-cis photoisomerization process concerning the cells fate. (01/01/2019 - 31/12/2019)
Task 3.1 - Evaluation of cell response as a function of the polymer chemical structure and surface relief profile in the case of azo-polymers with a stable relief in biological conditions.
Task 3.2 - Evaluation of cell response as a function of the polymer chemical structure and surface relief profile in the case of azo-polysiloxanes with a dynamic relief in biological conditions.
Task 3.3 - The study of the effect induced by the trans-cis photoisomerization process concerning the cells fate.
Task 3.4 - Evaluation nanostructuration processes of azo-polymeric films using pulse or continuous laser irradiation
The major objective of this project is to investigate cell-extracellular matrix interactions during cell growth on particular surfaces. These interactions can directly influence the cell-cycle, accelerating or slowing down cell division or induce cellular death by different mechanisms (apoptosis, autophagy, necrosis). In the case of stem cells, the mechanical signals transmitted by the substrate can induce specific cell differentiation and formation of artificial tissues. The mechanical signals are generated by the properties of the substrate, such as surface relief, elasticity and adhesion properties (essentially influenced by the chemical structure of the substrate), Azo-polymeric films enable laser manipulation of these surfaces, which promote them as ideal candidates for the studies proposed in this project. The film elasticity is influenced by the chemical structure of the core polymer chain, while adhesion properties are modulated by the azobenzene groups attached to the lateral chains. In addition, the azo-polysiloxanes enable the generation of a dynamic surface relief, which can adjust its geometrical parameters following the interaction with the biological environment. The cellular model used in this project is the undifferentiated (bipotent) HepaRG cell line; the ability of these cells to differentiate towards hepatic and biliary cells following culture on different azo-polymeric substrates will be monitored by specific molecular and microscopy analysis.
| Name of the budget category | Total Value 2017 (lei) | Total Value 2018 (lei) | Total Value 2019 (lei) | TOTAL Value (lei) |
|---|---|---|---|---|
| Staff expenses | 116.881,00 | 161.036,00 | 175.273,00 | 453.190,00 |
| Logistic costs | 100.000,00 | 78.000,00 | 75.302,00 | 253.302,00 |
| Mobilities costs | 6.782,00 | 11.651,00 | 16.292,00 | 34.725,00 |
| Indirect expenses | 31.149,00 | 35.339,00 | 42.295,00 | 108.783,00 |
| TOTAL | 254.812,00 | 286.026,00 | 309.162,00 | 850.000,00 |
1. Conformational analysis of polysiloxanes substituted with azobenzene, S. Ciobotarescu, E. L. Epure, N. Hurduc, Bul. Inst. Polit. Iasi, vol 63(67), 2, 2017
2. Folding time dependence of the motions of a molecular motor diluted inside an amorphous medium, S.Ciobotarescu, S. Bechelli, G. Rajanson, S. Migirditch, B. Hester, N. Hurduc, V. Teboul, Phys. Rev. E, 96, 062614, 2017
3. Molecular modeling study concerning the self-assembly capacity of some photosensitive amphiphilic polysiloxanes, E. L. Epure, N. Hurduc, A. Neamtu, in evaluation process
1. S. Ciobotarescu, E.L. Epure, C.M. Herghiligiu, N. Hurduc, Spatial arrangement of azobenzene substituted polysiloxane chains, 20th Romanian International Conference on Chemistry and Chemical Engineering – RICCCE 2017, 6 – 9 September, Poiana Brasov, Romania
2. C.M. Herghiligiu, S. Ciobotarescu, N. Nichita, D. Scutaru, N. Hurduc, Azo-polymers use in cell culture development, 20th Romanian International Conference on Chemistry and Chemical Engineering – RICCCE 2017, 6 – 9 September, Poiana Brasov, Romania
3. N. Hurduc, C.M. Herghiligiu, E. Luiza, D. Scutaru, Azopolymeric nanostructured films for biological applications, 4ème Colloque Franco-Roumain de Chimie Médicinale, 05 – 07 October 2017, Iasi, Romania.
4. E.L. Epure, N. Hurduc, Computational analysis on azopolymers capable to generate photo-sensitive micelles, IasiChem– Chemistry Faculty Conference, Al. Ioan Cuza University, 26-28.10.2017, Iasi, Romania
5. C.M. Herghiligiu, I. Carlescu, D. Scutaru, N. Hurduc, Dynamic azo-polymeric surfaces for cell culture application, IasiChem– Chemistry Faculty Conference, Al. Ioan Cuza University, 26-28.10.2017, Iasi, Romania
6. C.M. Herghiligiu, N. Hurduc, The possibility of controlled optical nanomanipulation of biomolecules, IasiChem– Chemistry Faculty Conference, Al. Ioan Cuza University, 26-28.10.2017, Iasi, Romania
7. I. Carlescu, A. Simion, G. Lisa, C. Herghiligiu, N. Hurduc, D.Scutaru, Synthesis and mesomorphic properties of 1,3,5-trisubstituted benzene derivatives containing azo-aromatic units as the peripheral arms, IasiChem– Chemistry Faculty Conference, Al. Ioan Cuza University, 26-28.10.2017, Iasi, Romania
8. S. Ciobotarescu, E.L. Epure, N. Hurduc, Azopolysiloxane conformational study through molecular modeling , IasiChem– Chemistry Faculty Conference, Al. Ioan Cuza University, 26-28.10.2017, Iasi, Romania